We have first studied the selective CO substitution reactions of heteronuclear tetrahedral clusters of the type (μ3-S)FeMCo(CO)^8(η~5-C^5H^4R)(M=Mo,W)with cyclohexyl isocyanide CyNC. It was found that while clusters(μ3-S)FeMCo(CO)^8(η~5-C^5H^4R)(M=Mo,W;R=MeCO)react with 1 equiv of CyNC in THF at room temperature to give mono-CyNC-substituted products (μ3-S)FeMCo(CO)^7(CyNC)(η~5-C^5H^4COMe)(1a,M=Mo;1b,M=W)in 63% and 79% yields, clusters of (μ3-S)FeMCo(CO)^8(η~5-C^5H^4R)(M=Mo,W;R=MeCO,MeO^2C,H)react with 2 equiv of cyNC under similar conditions to afford di-CyNC-substituted products (μ3-S)FeMCo(CO)^6(CyNC)^2(η~5-C^5H^4R)(2a,M=Mo;R=MeCO;2b,M=W,R=MeCO;2c,M=Mo,R=MeO^2C;2d,M=W,R=MeO^2C;2eM=MoR=h)in 56-68% yields. Similarly, tri-CyNC-substituted derivatives (μ3-S)FeMoCo(CO)^5(CyNC)^3(η~5-C^5H^4R)(3a,R=MeCO;3b,R=MeO^2C)are produced by reaction of clusters (μ3-S)FeMoCo(CO)^8(η~5-C^5H^4R)(R=MeCO,MeO^2C)with 3 equiv of CyNC in 37% and 39% yields. The combined use of spectroscopic techniques (IR, ~1H and ~59Co NMR, and ~57Fe Mossbauer spectroscopy) with crystal X-ray diffraction analyses for 1a, b and 2c d has established that the CyNC ligand in 1a, b is bonded to M (M=Mo,W), the two CyNC ligands in 2a-e are bound to M(Mo, W)and Fe, and the three CyNC ligands in 3a b are attached to Mo, Fe, and Co, respectively. Thus, the metallosite selectivity toward CyNCin the reaction of this type of cluster system decreases obviously in the order of η~5-RC^5H^4(CO)^2M(M=Mo,W) >Fe(CO)^3>Co(CO)^3